Worries about the potential negative consequences of popular fat loss regimens for aesthetic purposes in normal weight females have been surfacing in the media. However, longitudinal studies investigating these kinds of diets are lacking. The purpose of the present study was to investigate the effects of a 4-month fat-loss diet in normal weight females competing in fitness-sport. In total 50 participants finished the study with 27 females (27.2 ± 4.1 years) dieting for a competition and 23 (27.7 ± 3.7 years) acting as weight-stable controls. The energy deficit of the diet group was achieved by reducing carbohydrate intake and increasing aerobic exercise while maintaining a high level of protein intake and resistance training in addition to moderate fat intake. The diet led to a ~12% decrease in body weight (P < 0.001) and a ~35–50% decrease in fat mass (DXA, bioimpedance, skinfolds, P < 0.001) whereas the control group maintained their body and fat mass (diet × group interaction P < 0.001). A small decrease in lean mass (bioimpedance and skinfolds) and in vastus lateralis muscle cross-sectional area (ultrasound) were observed in diet (P < 0.05), whereas other results were unaltered (DXA: lean mass, ultrasound: triceps brachii thickness). The hormonal system was altered during the diet with decreased serum concentrations of leptin, triiodothyronine (T3), testosterone (P < 0.001), and estradiol (P < 0.01) coinciding with an increased incidence of menstrual irregularities (P < 0.05). Body weight and all hormones except T3 and testosterone returned to baseline during a 3–4 month recovery period including increased energy intake and decreased levels aerobic exercise. This study shows for the first time that most of the hormonal changes after a 35–50% decrease in body fat in previously normal-weight females can recover within 3–4 months of increased energy intake.

The accumulation of fat, especially in visceral sites, is a significant risk factor for several chronic diseases with altered cardiometabolic homeostasis. We studied how intensive long-term weight loss and subsequent weight regain affect physiological changes, by longitudinally interrogating the lipid metabolism and white blood cell transcriptomic markers in healthy, normal-weight individuals. The current study examined 42 healthy, young (age: 27.5 ± 4.0 years), normal-weight (body mass index, BMI: 23.4 ± 1.7 kg/m 2 ) female athletes, of which 25 belong to the weight loss and regain group (diet group), and 17 to the control group. Participants were evaluated, and fasting blood samples were drawn at three time points: at baseline (PRE); at the end of the weight loss period (MID: 21.1 ± 3.1 weeks after PRE); and at the end of the weight regain period (POST: 18.4 ± 2.9 weeks after MID). Following the weight loss period, the diet group experienced a ~73% reduction (~0.69 kg) in visceral fat mass (false discovery rate, FDR < 2.0 × 10 −16 ), accompanied by anti-atherogenic effects on transcriptomic markers, decreased low-grade inflammation (e.g., as α 1 –acid glycoprotein (FDR = 3.08 × 10 −13 ) and hs-CRP (FDR = 2.44 × 10 −3 )), and an increase in functionally important anti-atherogenic high-density lipoprotein -associated metabolites (FDR < 0.05). This occurred even though these values were already at favorable levels in these participants, who follow a fitness-lifestyle compared to age- and BMI-matched females from the general population (n = 58). Following the weight regain period, most of the observed beneficial changes in visceral fat mass, and metabolomic and transcriptomic profiles dissipated. Overall, the beneficial anti-atherogenic effects of weight loss can be observed even in previously healthy, normal-weight individuals.

Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., “semi-starvation”) leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 ± 4.0 years, body mass index 23.4 ± 1.7 kg/m 2 ) volunteered into either a diet group ( n = 25) or a control group ( n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline ( PRE ), at the end of the weight loss period ( MID 21.1 ± 3.1 weeks after PRE ), and at the end of the weight regain period ( POST 18.4 ± 2.9 weeks after MID ). In contrast to the control group, the diet group showed significant (false discovery rate <0.05) alteration of all measured immune function parameters—white blood cells (WBCs), immunoglobulin G glycome, leukocyte transcriptome, and cytokine profile. Integrative omics suggested effects on multiple levels of immune system as dysregulated hematopoiesis, suppressed immune cell proliferation, attenuated systemic inflammation, and loss of immune cell function by reduced antibody and chemokine secretion was implied after intense weight loss. During the weight regain period, the majority of the measured immune system parameters returned back to the baseline. In summary, this study elucidated a number of molecular pathways presumably explaining immunosuppression in individuals going through prolonged periods of intense training with low-energy availability. Our findings also reinforce the perception that the way in which weight loss is achieved (i.e., dietary restriction, exercise, or both) has a distinct effect on how the immune system is modulated.

Physique athletes lose substantial weight preparing for competitions, potentially altering systemic metabolism. We investigated sex differences in body composition, resting energy expenditure (REE), and appetite-regulating and thyroid hormone changes during a competition preparation among drug-free physique athletes. The participants were female (10 competing (COMP) and 10 non-dieting controls (CTRL)) and male (13 COMP) and 10 CTRL)) physique athletes. COMP were tested before they started their diet 23 weeks before competing (PRE), during their diet one week before competing (MID), and 23 weeks after competing (POST) whereas CTRL were tested at similar intervals but did not diet. Measurements included body composition by DXA, muscle size, and subcutaneous fat thickness (SFA) by ultrasound, REE by indirect calorimetry, circulating ghrelin, leptin T3, and T4 hormone analysis. Fat mass (FM) and SFA decreased in both sexes (p<0.001), while males (p<0.001) lost more lean mass (LM) than females (p<0.05). Weight loss, decreased energy intake, and increased aerobic exercise (p<0.05) led to decreased LM and FM-adjusted REE (p<0.05), reflecting metabolic adaptation. Absolute leptin levels decreased in both sexes (p<0.001) but more among females (p<0.001) due to higher baseline leptin levels. These changes occurred with similar decreases in T3 (p<0.001) and resting heart rate (p<0.01) in both sexes. CTRL, who were former or upcoming physique athletes, showed no systematic changes in any measured variables. In conclusion, while dieting, female and male physique athletes experience REE and hormonal changes leading to adaptive thermogenesis. However, responses seemed temporary as they returned toward baseline after the recovery phase. ClinicalTrials.gov (NCT04392752).

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